AU4977700A - Folic acid supplement - Google Patents
Folic acid supplement Download PDFInfo
- Publication number
- AU4977700A AU4977700A AU49777/00A AU4977700A AU4977700A AU 4977700 A AU4977700 A AU 4977700A AU 49777/00 A AU49777/00 A AU 49777/00A AU 4977700 A AU4977700 A AU 4977700A AU 4977700 A AU4977700 A AU 4977700A
- Authority
- AU
- Australia
- Prior art keywords
- folic acid
- based compounds
- compound
- magnesium
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 title claims description 340
- 235000019152 folic acid Nutrition 0.000 title claims description 207
- 239000011724 folic acid Substances 0.000 title claims description 207
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 title claims description 202
- 229960000304 folic acid Drugs 0.000 title claims description 202
- 239000013589 supplement Substances 0.000 title claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 191
- 239000002253 acid Substances 0.000 claims description 169
- 230000003472 neutralizing effect Effects 0.000 claims description 127
- 239000000203 mixture Substances 0.000 claims description 103
- 231100000252 nontoxic Toxicity 0.000 claims description 90
- 230000003000 nontoxic effect Effects 0.000 claims description 90
- -1 folic acid compound Chemical class 0.000 claims description 81
- 241001465754 Metazoa Species 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 50
- 235000015872 dietary supplement Nutrition 0.000 claims description 48
- 239000011777 magnesium Substances 0.000 claims description 39
- 229910052749 magnesium Inorganic materials 0.000 claims description 39
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 38
- 238000010521 absorption reaction Methods 0.000 claims description 32
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 29
- 229910052782 aluminium Inorganic materials 0.000 claims description 24
- 235000016709 nutrition Nutrition 0.000 claims description 24
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 23
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 23
- 239000011575 calcium Substances 0.000 claims description 23
- 229910052791 calcium Inorganic materials 0.000 claims description 23
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 21
- 239000011734 sodium Substances 0.000 claims description 21
- 229910052708 sodium Inorganic materials 0.000 claims description 21
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 20
- 229940069428 antacid Drugs 0.000 claims description 20
- 239000003159 antacid agent Substances 0.000 claims description 20
- 239000011591 potassium Substances 0.000 claims description 20
- 229960003975 potassium Drugs 0.000 claims description 20
- 229910052700 potassium Inorganic materials 0.000 claims description 20
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 19
- 239000003826 tablet Substances 0.000 claims description 18
- 208000010188 Folic Acid Deficiency Diseases 0.000 claims description 14
- 206010016880 Folate deficiency Diseases 0.000 claims description 13
- PPQREHKVAOVYBT-UHFFFAOYSA-H dialuminum;tricarbonate Chemical compound [Al+3].[Al+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O PPQREHKVAOVYBT-UHFFFAOYSA-H 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 10
- 239000011159 matrix material Substances 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 235000015424 sodium Nutrition 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 7
- 239000007910 chewable tablet Substances 0.000 claims description 7
- 229940004916 magnesium glycinate Drugs 0.000 claims description 7
- 239000007938 effervescent tablet Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- 229910000014 Bismuth subcarbonate Inorganic materials 0.000 claims description 5
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 claims description 5
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 claims description 5
- 229910000323 aluminium silicate Inorganic materials 0.000 claims description 5
- 229940118662 aluminum carbonate Drugs 0.000 claims description 5
- UTUUIUQHGDRVPU-UHFFFAOYSA-K aluminum;2-aminoacetate;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Al+3].NCC([O-])=O UTUUIUQHGDRVPU-UHFFFAOYSA-K 0.000 claims description 5
- SEIGJEJVIMIXIU-UHFFFAOYSA-J aluminum;sodium;carbonate;dihydroxide Chemical compound [Na+].O[Al+]O.[O-]C([O-])=O SEIGJEJVIMIXIU-UHFFFAOYSA-J 0.000 claims description 5
- 229940104825 bismuth aluminate Drugs 0.000 claims description 5
- 229940036348 bismuth carbonate Drugs 0.000 claims description 5
- MGLUJXPJRXTKJM-UHFFFAOYSA-L bismuth subcarbonate Chemical compound O=[Bi]OC(=O)O[Bi]=O MGLUJXPJRXTKJM-UHFFFAOYSA-L 0.000 claims description 5
- 229940036358 bismuth subcarbonate Drugs 0.000 claims description 5
- JAONZGLTYYUPCT-UHFFFAOYSA-K bismuth subgallate Chemical compound OC(=O)C1=CC(O)=C2O[Bi](O)OC2=C1 JAONZGLTYYUPCT-UHFFFAOYSA-K 0.000 claims description 5
- 229960000199 bismuth subgallate Drugs 0.000 claims description 5
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 claims description 5
- 239000001354 calcium citrate Substances 0.000 claims description 5
- 229940092124 calcium citrate malate Drugs 0.000 claims description 5
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 5
- 239000000920 calcium hydroxide Substances 0.000 claims description 5
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 5
- 235000011116 calcium hydroxide Nutrition 0.000 claims description 5
- 239000001506 calcium phosphate Substances 0.000 claims description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims description 5
- MPCMQXRREZMSPJ-UHFFFAOYSA-L calcium;2-hydroxybutanedioate;2-hydroxypropane-1,2,3-tricarboxylic acid;pentahydrate Chemical compound O.O.O.O.O.[Ca+2].[O-]C(=O)C(O)CC([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O MPCMQXRREZMSPJ-UHFFFAOYSA-L 0.000 claims description 5
- 229940068682 chewable tablet Drugs 0.000 claims description 5
- GMZOPRQQINFLPQ-UHFFFAOYSA-H dibismuth;tricarbonate Chemical compound [Bi+3].[Bi+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O GMZOPRQQINFLPQ-UHFFFAOYSA-H 0.000 claims description 5
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 claims description 5
- 229940015828 dihydroxyaluminum sodium carbonate Drugs 0.000 claims description 5
- 229940014144 folate Drugs 0.000 claims description 5
- PDSAKIXGSONUIX-UHFFFAOYSA-N hexaaluminum;dibismuth;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Bi+3].[Bi+3] PDSAKIXGSONUIX-UHFFFAOYSA-N 0.000 claims description 5
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 5
- 239000001095 magnesium carbonate Substances 0.000 claims description 5
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 5
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 5
- 239000000347 magnesium hydroxide Substances 0.000 claims description 5
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 5
- 239000000395 magnesium oxide Substances 0.000 claims description 5
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 5
- 235000012245 magnesium oxide Nutrition 0.000 claims description 5
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 239000001508 potassium citrate Substances 0.000 claims description 5
- 229960002635 potassium citrate Drugs 0.000 claims description 5
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 5
- 235000011082 potassium citrates Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 235000017550 sodium carbonate Nutrition 0.000 claims description 5
- 239000001509 sodium citrate Substances 0.000 claims description 5
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 5
- 235000013337 tricalcium citrate Nutrition 0.000 claims description 5
- ZUGAOYSWHHGDJY-UHFFFAOYSA-K 5-hydroxy-2,8,9-trioxa-1-aluminabicyclo[3.3.2]decane-3,7,10-trione Chemical compound [Al+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZUGAOYSWHHGDJY-UHFFFAOYSA-K 0.000 claims description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 4
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 claims description 4
- 235000010216 calcium carbonate Nutrition 0.000 claims description 4
- 239000001488 sodium phosphate Substances 0.000 claims description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 4
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 4
- 229940088623 biologically active substance Drugs 0.000 claims description 3
- 235000011181 potassium carbonates Nutrition 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- 235000011083 sodium citrates Nutrition 0.000 claims description 3
- 235000011008 sodium phosphates Nutrition 0.000 claims description 3
- 229910052797 bismuth Inorganic materials 0.000 claims description 2
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 2
- 229940125758 compound 15 Drugs 0.000 claims description 2
- 229940125810 compound 20 Drugs 0.000 claims description 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims description 2
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 claims 4
- 239000000391 magnesium silicate Substances 0.000 claims 4
- 229940099273 magnesium trisilicate Drugs 0.000 claims 4
- 229910000386 magnesium trisilicate Inorganic materials 0.000 claims 4
- 235000019793 magnesium trisilicate Nutrition 0.000 claims 4
- AACACXATQSKRQG-UHFFFAOYSA-L magnesium;2-aminoacetate Chemical compound [Mg+2].NCC([O-])=O.NCC([O-])=O AACACXATQSKRQG-UHFFFAOYSA-L 0.000 claims 4
- 229940001593 sodium carbonate Drugs 0.000 claims 4
- HWSISDHAHRVNMT-UHFFFAOYSA-N Bismuth subnitrate Chemical compound O[NH+]([O-])O[Bi](O[N+]([O-])=O)O[N+]([O-])=O HWSISDHAHRVNMT-UHFFFAOYSA-N 0.000 claims 3
- 229960001482 bismuth subnitrate Drugs 0.000 claims 3
- 229960003563 calcium carbonate Drugs 0.000 claims 3
- MPRVXUYAJZZBHG-UHFFFAOYSA-K dicarbonoperoxoyloxyalumanyl hydroxy carbonate Chemical compound [Al+3].OOC([O-])=O.OOC([O-])=O.OOC([O-])=O MPRVXUYAJZZBHG-UHFFFAOYSA-K 0.000 claims 3
- 229940093956 potassium carbonate Drugs 0.000 claims 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 2
- 229960004256 calcium citrate Drugs 0.000 claims 2
- 229940095643 calcium hydroxide Drugs 0.000 claims 2
- 229960001714 calcium phosphate Drugs 0.000 claims 2
- 229940125773 compound 10 Drugs 0.000 claims 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims 2
- 229960001708 magnesium carbonate Drugs 0.000 claims 2
- 229960000816 magnesium hydroxide Drugs 0.000 claims 2
- 229960000869 magnesium oxide Drugs 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 235000021317 phosphate Nutrition 0.000 claims 2
- 229940083542 sodium Drugs 0.000 claims 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- NKCVNYJQLIWBHK-UHFFFAOYSA-N carbonodiperoxoic acid Chemical compound OOC(=O)OO NKCVNYJQLIWBHK-UHFFFAOYSA-N 0.000 claims 1
- 235000012254 magnesium hydroxide Nutrition 0.000 claims 1
- 229940093916 potassium phosphate Drugs 0.000 claims 1
- 229960001790 sodium citrate Drugs 0.000 claims 1
- 229960003339 sodium phosphate Drugs 0.000 claims 1
- 231100000331 toxic Toxicity 0.000 claims 1
- 230000002588 toxic effect Effects 0.000 claims 1
- 229940088594 vitamin Drugs 0.000 description 20
- 239000011782 vitamin Substances 0.000 description 20
- 229930003231 vitamin Natural products 0.000 description 17
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- 230000007812 deficiency Effects 0.000 description 11
- 239000003814 drug Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
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- 210000001035 gastrointestinal tract Anatomy 0.000 description 7
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- 150000003722 vitamin derivatives Chemical class 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 5
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/174—Vitamins
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Polymers & Plastics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Inorganic Chemistry (AREA)
- Animal Husbandry (AREA)
- Physiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Description
WO00/66083 PCTUS00/1 1688 FOLIC ACID SUPPLEMENT BACKGROUND OF THE INVENTION Field of the Invention 5 The present invention is directed to novel chewable or dissolvable nutritional supplements in imprroved forms that optimize absorption of folic acid in humans and other animals, and methods of using said supplements. The nutritional supplements are 10 formulated with folic acid and non-toxic acid neutralizing alkaline compounds in chewable or dissolvable forms which provide highly absorbable or highy bioavailable forms of folic acid. 15 Description of the Related Art Foic acid deficiency is the most common vitamin deficiency experienced by individuals in the United States. See USP DTI m Drug Information for the Health Care Pro'fessional 18 Ed., 1998. It is crucia that 20 an adecuaze level of folic acid be maintained in the body because foli acid clays an esceciall im
'
oortant physiological role. Folic acid, also known as WO00/66083 PCTUS00/1 1688 pteroylglutamic acid and vitamin B 9 , plays an important role in cell division, erythropoiesis and protein synthesis, all of which are processes very important to growing tissues. Folic acid is part of an enzyme 5 complex that changes vitamin B- into its active form and helps synthesize amino acids into the new DNA required for dividing cells. See Whitney, E. and Rolfes, S., Understanding Nutrition, 6-' Ed., 311 (1993). Folic acid delivered to the body in food is 10 often bound to glutamic acid, but the body prefers to absorb the folic acid in its "free" state. Therefore, folic acid has a low bioavailability. Id. In fact, only about half of dietary folic acid is available to the body. The Recommended Daily Allowance 15 (RDA) for folic acid takes this low bioavailabilitv into account. For example, in the United States, the RDA for folic acid is as follows: 150-200 mcg for adult males, 150-180 mcg for adult: females, 400 mc; for pregnant females, 260-280 mcg for lactating women and 20 25-50 mco for infan
-
ts and children. See C.rrent edia:rl Diagnosis and Trearmen:, Ed., 199. 2 WO00/66083 PCT/US00/1 1688 Uncooked green vegetables, beans, liver, kidney, yeast, potatoes, cereal, mushrooms and fruit juices are all sources of folic acid. However, the heating of foods will destroy up to 90% of the bioavailable folic 5 acid. See Whitney, E. and Rolfes, S., Understanding Nutrition, 6
:
' Ed., 314 (1993). Therefore, natural sources of folic acid provide a low bioavailable or poorly absorbable form of folic acid. Various internal and external factors can result 10 in folic acid deficiencies in both males and females. For example, folic acid deficiency can occur when there is a need for increased cell proliferation, such as that experienced during pregnancy, cancer, blood loss and skin diseases. Folic acid is also very vulnerable 15 to interactions with drugs. Drugs with similar chemical structures to folic acid, can replace folic acid in metabolic pathways. For example, aspirin, antacids, cholestyramine, anticonvulsants and oral contracectives may interfere with the levels of folic 20 acid in body tissues. Various other factors can also necativelv imoaco folic acid levels, for example, smoking and prolonged stress. Id. a: 33. 3 WO00/66083 PCTUS00/1 1688 Further, folio acid is converted into an active form in the liver and is absorbed by the intestinal system. As a result, folate metabolism is vulnerable to any intestinal system disturbance, such as injury to 5 GI tract cells or alcohol abuse. Id. Regardless of the cause, folio acid deficiency carries serious consequences. Specifically, folic acid deficiency impairs cell division and protein synthesis. Further, folio acid deficiency slows the replacement of 10 red blood cells and GI tract cells. A significant symptom of folio acid deficiency is anemia, including megaloblastic anemia and macrocytic anemia. Id. The physiological demands for folic acid are elevated when additional stresses are placed upon the 15 body. For instance, due to the increase in cell proliferation during a pregnancy, pregnant women require more folic acid than normal, and are at a greater risk for a folic acid deficiency. Therefore, the recommended intake of folic acid is increased 20 during orecnancyv. In view of this increased risk, physicians generally recommend that pregnant women supplement their diet with vitamin and mineral WO 00/66083 PCTUS00/1 1688 formulations. Folic acid supplementation during pregnancy is believed to reduce the risk of neural tube defects, such as spina bifida, in infants. See Current bstretrics and Gynecology Diagnosis and Treatment, 86 5 Ed., 1994. Other teratogenic effects (e.g. birth defects) are linked to underexposure to folic acid or overexposure to folic acid antagonists. See Current Pediatric Diagnosis and Treatment, 13 Ed., 1997. Various approaches to increasing the 10 bioavailability of folic acid have been described. Further, numerous approaches for reducing the risk of neural tube defects and other birth defects have also been described in several references. For example, Nesbitt, U.S. Patent No. 5,569,477, 15 discloses a chewing gum containing various vitamins and minerals, including folic acid. The vitamins and minerals are preferably present in levels prescribed by the U.S. RDA. Sercelloni et al., U.S. Patent No. 5,527, 542 , 20 disclose a process for coating the surface af vitamin and other pharmaceuticals products with Mal:itol sugar, to improve che taste and aesthetic appearance of the 5 WO 00/66083 PCTUS00/1 1688 product. Whether in tablet or form, the products would be intended to be swallowed whole. Sparks et al., U.S. Patent No. 4,952,402, disclose a controlled release powder made of microparticles 5 containing an active ingredient, such as vitamins or pharmaceuticals, and a polymer. The powder can be suspended in licuid and maintain its controlled release characteristics for a sustained period of time. Callingham et al., U.S. Patent No. 5,028,411, 10 disclose a composition for the buccal or nasal administration of iron, zinc and folic acid to the body. The buccal and nasal sprays and lozenges of this invention are made of a neutral iron(III) complex, which is more effective in the neutral pH of the mouth 15 and nose than in the gastrointestinal tract. Mehra et al., U.S. Patent No. 5,733,575, disclose a non-toxic enteric film coating for pharmaceuticals comprising a polymer, a detackifier, a viscosity modifier and an alkalizing agent. The coating prevents 20 the active inaredient from being absorbed by tnhe body until it reaches the intestines. 6 WO00/66083 PCTUS00/1 1688 Briggs et al., U.S. Patent No. 4,752,479, describe a mul-i-vitamin and mineral supplement for oral administration containing divalent calcium and magnesium as well as iron. The mineral supplement is 5 adapted to be released in the upper gastrointestinal tract, while the iron component is adapted to be released in the lower intestinal tract. Vitamin supplements for pregnant women containing folic acid have also been described in various 10 references. Uterwaal et al., U.S. Patent No. 4,710,38, describe a nutritional supplement for pregnant and breast-feeding women based on milk constituents containing, among other vitamins and minerals, folic acid. 15 Paradissis et al., U.S. Patent No. 5,494,678, disclose a muci-vitamin and mineral supplement for pregnant women comprising a regimen of calcium, vitamin D and certain B complex vitamins, including folic acid. This supplement is tailored to maximize fetal 20 developmen: and maternal health during pregnancy. The Physician's Desk Reference for Nonprescrip~tion Drugs describes vari-ous vitamin and mineral supplements WO00/66083 PCT/US00/1 1688 which contain folic acid. For example, One-A-Day® Maximum Formula Vitamins and Minerals for Adults, made by Miles, Inc., is a multi-vitamin and mineral supplement indicated as a dietary pill to be swallowed 5 once a day. The supplement contains 0.4 mg of folic acid. See Physician's Desk Reference for Nonprescripticn Drugs, 611 (9 1 h Ed., 1988). Vitamins for Women, made by Vitamins focr Women, Inc., is a set of vitamin and mineral supplements, one 10 to be taken during the day and the other at night. The supplements contain 400 mcg of folic acid. See Physician's Desk Reference for Nonprescription Drugs, 718 (9: Ed., 1988). Theragren Jr.0, made by E.R. Squibb and Sons, 15 Inc., is a children's chewable vitamin formula. The chewable supplements contains 0.4 mg of folic acid. See Physician's Desk Reference for Nonprescription Drugs, 705 (9t Ed., 1988). Flintstones® Complete and Bugs Bunny@ Children's 20 Chewable Vioamins, made by Miles Inc., is a chil-dren's chewable vitamins dietarv suclement. These chewable supplements both contain 0.3 mg of folic acid. See WO 00/66083 PCT/US00/11688 Physician's Desk Reference for Nonprescription Drugs, 610 (9 , Ed., 1988). The above described folic acid compositions and methods are deficient in that they fail to provide 5 highly absorbable folic acid. Further, the current formulations and methods do not adequately address folic acid deficiency, particularly in individuals with enhanced folio acid requirements, such as women who are pregnant. 10 Folic acid is poorly absorbed when it is not solubulized in the intestines. In the above described folic acid compositions, the folic acid is delivered to the body in dosage forms that leave folic acid in a poorly solubilized state due to the stomach's acidic 15 environment. As capsules and tablets are broken down by the stomach's digestive acids, the folic acid is precipitated and thus converted to a form that is less soluble. Therefore, very little folic acid in a soluble form reaches the intestines. Even the folic 20 acid which does reach the intestines encounters problems with absorption.
Q
WO00/66083 PCT/US00/1 1688 As discussed above, folic acid plays an essential role in various physiological processes. Previously available forms of folic acid do not optimize absorption of folic acid. Accordingly, it would be 5 desirable to provide a nutritional supplement containing folic acid which overcomes the deficiencies of the previously-available folic acid supplements. In particular, there is a need for folic acid supplements which optimize or improve the absorption of folic acid. 10 SUMMARY OF THE INVENTION The present invention provides improved folio acid supplements for both men and women. The present supplements overcome the deficiencies of current folio 15 acid supplements by providing a formulation which improves or optimizes the absorption of folic acid. The supplement also provides folic acid in a highly absorbable form. The present invention is based ucon the unexpected discovery that folic acid absorption is 20 increased when folic acid is provided in a chewable or dissolvable form in combination wi h a non-coxic acid neutralizine compound. 10 WO00/66083 PCTUS00/ 1688 Without being limited by theory, the chewing or dissolving action in this form, activates the acid neutralizing agent(s) in the mouth, thereby creating an acid neutralizing environment for the folio acid. This 5 interaction continues as the composition moves into the stomach continuing to neutralize the digestive acids of this environment, thereby providing the preferably absorbable form of folic acid to the intestinal tract where it is absorbed into the body. 10 The nutritional supplements of the invention comprise stable chewable or dissolvable forms. In one embodiment of the present invention, the stable chewable or dissolvable forms include a non-toxic acid neutralizing alkaline compound combined with a folic 15 acid compound or derivative thereof, where te= non toxic acid neutralizing alkaline compound has a total daily dosace of at least 2 mea of acid neutralizing capacity, and the folic acid compound or dervat ive thereof has a total daily dosage of at least 450 mcg. 20 An alternative embodiment of the invention is a nutrizional supclemen . . cpimiing cr improving absorption of folic acid in an animal, which comprises WO00/66083 PCTUS00/ 1688 a stable chewable or quickly dissolvable form including a non-toxic acid neutralizing alkaline compound surrounding a folio acid compound or derivative thereof, wherein the non-toxic acid neutralizing 5 alkaline compound has a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folio acid compound or derivative thereof has a total daily dosage of at least 450 mcg. Another embodiment of the invention is a prenatal 10 nutritional supplement for optimizing the absorption of folic acid in a pregnant woman and the fetus, which comprises a stable chewable or quickly dissolvable form including a non-toxic acid neutralizing alkaline compound surrounding a folic acid compound or 15 derivative thereof, wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at least 2 meq of acid neutralizing capacity, and the fo l c acid compound or derivative therecf has a total daily dosage of at least 500 mcg. 20 A further embodiment of the invention is a orenatal chewable nutritional supplement for cp-imizing absortion of folic acid in a pregnant woman, which 12 WO00/66083 PCTUS00/1 1688 comprises a stable chewable form comprising a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, 5 sodium-based compounds, potassium-based compounds and mixtures thereof surrounding a folio acid compound or derivative thereof, wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at least 2 meq of acid neutralizing capacity, and 10 the folic acid compound or derivative thereof has a total daily dosage at least 500 mcg. The present invention is also directed to a nutritional regimen for optimizing absorption of folic acid. One embodiment of the nutritional regimen 15 comprises a stable chewable or quickly dissolvable form comprising a non-toxic acid neutralizing alkaline compound surrounding a folio acid compound or derivative thereof, wherein the non-toxic acid neutralizing alkaline compound is present in said 20 regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound 13 WO00/66083 PCT/US00/1 1688 or derivative thereof is present in said regimen in a total daily dosage greater of at least 450 mcg. An alternative embodiment of the nutritional regimen for optimizing absorption of folio acid in an 5 animal comprises a stable chewable form comprising a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based 10 compounds and mixtures thereof surrounding a folic acid compound or derivative thereof, wherein the non-toxic acid neutralizing alkaline compound is present in said regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound 15 or derivative thereof has a total daily dosage of at least 450 mcg. Another embodiment of the nutritional regimen for optimizing absorption of: folic acid in a pregnant woman comprises a stable chewable form comorising a non-toxic 20 acid neutralizing alkaline comound selected from the group cnsissting of calcium-basec compounds, antacids, aluminum-based compounds, magnesium-based compounds, 14 WO00/66083 PCTUS00/1 1688 sodium-based compounds, potassium-based compounds and mixtures thereof surrounding a folic acid compound or derivative thereof, wherein the non-toxic acid neutralizing alkaline compound is present in said 5 regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound or derivative thereof has a total daily dosage of at least 500 mcg. The present invention is also directed to methods 10 of optimizing the absorption of folic acid in animals. In one embodiment the method of the present invention comprises administering at least once during a day to the animal a stable chewable form comprising a folic acid compound or derivative thereof in combination with 15 a non-toxic acid neutralizing alkaline compound. The total dosage of said folic acid compound or derivative thereof administered during the day is at least 450 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the 20 day has at least 2 meq of acid neutralizing capacity. in an alternative embodiment, the method of oimizing foli acid absortion comprises 15 WO00/66083 PCTUS00/1 1688 administering at least once during a day to the animal a stable chewable form comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound, wherein the total 5 dosage of said folic acid compound or derivative thereof administered during the day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizinc alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 10 In another embodiment, the method of optimizing the absorption of folic acid comprises administering at least once a day to a mammal a stable chewable form comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing 15 alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds and mixtures thereof, wherein the folic acid compound or derivative 20 thereof has a total daily dosage of at least 500 mcg, and the non-toxic acid neutralizing alkaline comound 16 WO00/66083 PCTUS00/1 1688 is present in said regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity. Another objective of the present invention is to provide methods of preventing or treating folic acid 5 deficiency in pregnant women. One embodiment of the method of preventing or treating folic acid deficiency in pregnant women comprises administering at least once during a day to the animal a stable chewable form comprising a folic acid compound or derivative thereof 10 in combination with a non-toxic acid neutralizing alkaline compound, wherein the total dosage of said folic acid compound or derivative thereof administered during the day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline 15 compound administered during the day has at least 2 meq of acid neutralizing capacity. An alternative embodiment of the method of preventing or treating folic acid deficiency in an animal comprises administering at least once during a 20 day to the animal a stable chewable form comprising a folic acid compound or derivative thereof in comb.ination wi:th a non-toxic acid neutralizing alkaline 17 WO00/66083 PCTUS00/1 1688 compound, wherein the total dosage of said folic acid compound or derivative thereof administered during the day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound 5 administered during the day has at least 2 meq of acid neutralizing capacity. In a further embodiment of the invention, a method of preventing or treating folic acid deficiency in a pregnant woman comprises administering at least once a 10 day to the pregnant woman a stable chewable form comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based 15 compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds and mixtures thereof, wherein the folic acid compound or derivative thereof has a total daily dosage of at least 500 mcg, and the non-toxic acid neutralizing alkaline compound 20 is present in said regimen in a total daily dosage of at least 2 mea of acid neutralizing capacity. 18 WO00/66083 PCTIUS00/1 1688 In a still further embodiment of the invention, a method of preventing or treating folic acid deficiency in a pregnant woman comprises administering at least once a day to the pregnant woman a stable chewable form 5 comprising a folic acid compound in combination with a non-folate biologically active substance and a non toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based 10 compounds, sodium-based compounds, potassium-based compounds and mixtures thereof, wherein the folic acid compound or derivative thereof has a total daily dosage of at least 500 mcg, and the non-toxic acid neutralizing alkaline compound is present in said 15 regimen in a total daily dosage of at least 2 mea of acid neutralizing capacity. In an additional embodiment of the invention, a method of preventing or treating a condition in an animal is provided which com-rises admiistering at 20 least once during a day to the animal a stable chewable or dissolvable form comrisin a folic acid compound or derivative thereof in combination with a non-toxic acid 19 WO00/66083 PCTUS00/1 1688 neutralizing alkaline compound; wherein the total dosage of said folic acid compound or derivative thereof administered during the day is at least 450 mcg, and the total dosage of said non-toxic acid 5 neutralizing alkaline compound administered during the day has a: least 2 meq of acid neutralizing capacity. DETAILED DESCRIPTION OF THE INVENTION As used herein, "animal" refers to a human, mammal 10 or any other animal. "Active site" refers to the location where an active substance must be present to have its intended effect. "Form" refers to one discrete unit containing a 15 designated amount of the composition of the invention. "Dissolvable form" refers to any forms which dissolve in the mouth and/or esophagus after oral ingestion. "Chewable form" refers to any forms which are 20 chewed in the mouth after oral inaestion. "Acid neu:ralizinc capacity" is the amount, in milliequivalenzs (meq), of an alkaline substance that 20 WO00/66083 PCTUS00/1 1688 will neutralize a specific amount, in millieauivalents (meq), of acid. The present invention is based upon the unexpected discovery that greater absorption of folic acid is 5 achieved when the folic acid is combined with a non toxic acid neutralizing alkaline compound in a chewable or quickly dissolvable form. Without being limited by theory, one explanation for this is that the pre wetting of the acid neutralizing alkaline compound in 10 the mouth initiates an interaction between the folic acid compound and the non-toxic acid neutralizing alkaline compound which continues as the composition moves through the digestive system. Thus, the chewing or dissolving action in this form, activates the acid 15 neutralizing agent(s) in the mouth, thereby creating an acid neutralizing environment for the folic acid. This interaction continues as the composition moves into the stomach continuing to neutralize the digestive acids of this environment, thereby providing the preferably 20 absorbable form of folic acid to the intestinal tract where it is absorbed into the body. Thus, the interaction between the folic acid and non-toxic acid 21 WO00/66083 PCTUS00/1 1688 neutralizing alkaline compound, when administered in a chewable or dissolvable form, facilitates absorption of folic acid because a critical interaction is initiated by the chewing action or dissolving activity in the 5 mouth. The present invention provides an improved folic acid composition which provides a more absorbable form of folic acid. The present compositions are superior to previously-available forms of folic acid in that 10 they result in improved folic acid absorption. In particular, the nutritional supplement of the present invention contains folic acid or a derivative thereof in combination with a non-toxic acid neutralizing compound in a chewable or dissolvable form. 15 The non-toxic acid neutralizing alkaline compounds for incorporation into the compositions of the present invention include, natural and synthetic alkaline compounds and compounds that react like alkaline compounds, for example, without limitation, calcium 20 based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, proteins, amino acids, WO00/66083 PCTUS00/1 1688 Attorney Docket No. 23729 fermented products and mixtures thereof. Further non limiting exemplary non-toxic acid neutralizing alkaline compounds include aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum hydroxy 5 carbonate, aluminum citrate, dihydroxyaluminum sodium carbonate, aluminum magnesium glycinate, dihydroxyaluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth 10 subnitrate, calcium carbonate, calcium hydroxide, calcium phosphate, calcium citrate, calcium citrate malate, hydrated magnesium aluminate, activated sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium 15 glvcinate, magnesium hydroxide, magnesium oxide, magnesium tr1silicate, potassium carbonate, potassium phosphate, potassium citrate, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium citrate and mixtures thereof. 20 Preferably, the compositions of the present nventicon coni a east 2 meq of acid neu-r:=izing capacity of che non-coxic acid neutralizing alkaline 2 3 WO00/66083 PCTUS00/1 1688 composition. More preferably, the compositions of the present invention contain at least 5 meq of the non toxic acid neutralizing alkaline composition. Even more preferably, the compositions of the present 5 invention contain at least 10 meq of the non-toxic acid neutralizing alkaline composition. For example, without limitation, when the non toxic acid neutralizing alkaline compound is calcium carbonate, preferably, at least 100 mg of calcium 10 carbonate is present in the composition. More preferably, the amount of calcium carbonate present is at least 200 mg. Even more preferably, the amount of calcium carbonate present is at least 250 mc. Still more preferably, the calcium carbonate present is at 15 least 400 mg. Most preferably, the calcium carbonate present is at least 500 mg. The compositions of the present invention include a folic acid compound or derivative thereof. The derivatives of folic acid include compounds formed from 20 folic acid which may be structuraliv distinct from folic acid, but which retain the active function of folic acid. Non-limitina examoes of such derivatives 24 WO00/66083 PCTUS00/1 1688 include salts of folic acid, alkaline salts of folio acid, esters of folic acid, chelates of folic acid and combinations thereof. Preferably, the compositions of the present 5 invention contain a total daily dosage of greater than 450 mcg of a folic acid compound or derivative thereof. More preferably, the compositions of the present invention contain a total daily dosage of at least 500 mcg of a folic acid compound or derivative thereof. 10 Even more preferably, the compositions of the present invention contain a total daily dosage of at least 600 mcg of a folic acid compound or derivative thereof. Most preferably, the compositions of the present invention contain a total daily dosage of at least 15 1,000 mcg o: a folic acid compound or derivative thereof. The nutritional supplement is comprised of a stable chewable or dissolvable form. The form may be i any chewable or dissolvable form. Pre-fer=by, the 20 dissolvable form will dissolve within thirwy seconds of oral ingestion. Non-limiting exemplar- forms of the Present invention include chewable tablets, quick 25 WO00/66083 PCTUS00/1 1688 dissolve tablets, effervescent tablets, particulate matrices, microparticulate matrices, health bars, confections, liquids, foods, animal feeds, cereal coatings, cereals, food supplements, nutritional 5 supplements, functional foods, nutritive foods and mixtures thereof. The form comprises a non-toxic acid neutra-lizing alkaline compound combined with a folic acid compound or folio acid derivative and any necessary additive required to achieve a quick dissolve 10 or chewable structure. The folic acid may be physically separated from the non-toxic acid neutralizing alkaline compound so that the compounds do not come into contact with one another until after ingestion. 15 The abilityv to obtain chewable or dissolvable forms is performed using well known procedures and techniques available to the ordinary skilled artisan. Each of these specific techniques or procedures for obtaining these structural characteristics do not in 20 themselves constitute an inventzive aspect of this invention. 26 WO00/66083 PCTUS00/I 1688 For example, dissolvable tablets, without limitation, may prepared by combining active components with sugars and cellulose derivatives to form a uniform mixture which is then formed into compressed tablets. 5 The compressed tablets may be formed through direct compression or granulation and then compression, without limitation. The process thus employed can provide a tablet that dissolves or disintegrates after oral administration, and generally within 30 seconds. 10 Chewable tablets, without limitation, may be prepared by combining various excipients, such as binders, flavorings, colorants and the like, with active components to form relatively soft, flavored, tablets that can be chewed rather than swallowed whole. 15 Conventional tablet machinery and procedures (both direct compression and granulation) can be utilized. Chewable forms may also be prepared by molding a mixture into a shaped form, immersing the dose forms in a calcium icn bath, recovering the dose forms from the 20 bath, rinsing the dose forms and packaging the dose forms for use. See Vellekoo at al., U.S. Patent 4,765,984. The ui dose forms may be individually wrapped, packaged as multiple units on paper strips or WO 00/66083 PCTUS00/1 1688 in vials of any size, without limitation. The chewable and dissolvable tablets of the invention may be packaged in unit dose, rolls, bulk bottles, blister packs and combinations thereof, without limitation. 5 Health bars, without limitation, may be prepared by combining various excipients, such as binders, fillers, flavorings, colorants and the like, along with active components, and mixing to a plastic mass consistency. The mass is then either extruded or 10 molded to form "candy bar" shapes that are then dried or allowed to solidify to form the final product. Animal feeds, without limitation, may be prepared by combining active components with binding ingredients to form a plastic mass. The mass is then extruded 15 under high pressure to form tubular (or "spaghetti like") structures that are cut to pellet size and dried. Cereal or cereal coatings, without limi :ation, may be prepared by forming the active components into 20 pelletrs, flakes or other geometric shapes. The cellets, flakes or other geometric shares are then passed under a precision spray coating device to deposit a film of active ingredients plus excipients Oq WO00/66083 PCT/US00/I 1688 onto the surface of the formed elements. The units thus treated are then dried or allowed to dry. The compositions described herein are intended for administration to any animal. The compositions are 5 preferably administered to mammals. More preferably, the compositions are administered to humans. The compositions are intended to be administered to both females or male. Further, the compositions can be administered to both pregnant and non-pregnant women. 10 Pregnant women have an enhanced need for folic acid, to prevent anemia and reduce the risks of birth defects. The combination of the folic acid with the non toxic acid neutralizing alkaline compound in the chewable or dissolvable forms is very effective with 15 regard to increasing the absorption of folic acid. While it is difficult to quantify the effectiveness of the Formulations. Preferably, the percentage of folic acid absorbed from an animal's gastrointestinal tract after administration of the form relative to the amount 20 of folic acid in the chewable or dissolvable form is at least 45% defending upon intervening external or internal factors. More preferably, the percentage absorbed is at least 55%. Even more preferably, the 29 WO00/66083 PCT/US00/ 1688 percentage absorbed is at least 70%. Still more preferably, the percentage absorbed is at least 85%. Most preferably, the percentage absorbed is at least 95%. 5 Various additive may also be incorporated into the present compositions. Non-limiting examples of additives of the present invention include calcium carbonate, compressible sugar, particulate composite coating, flavorings and magnesium stearate. 10 The present invention also provides a prenatal nutritional supplement for optimizing the absorption of folic acid in a pregnant woman, as well as methods for optimizing absorption of folic acid and treating folio acid deficiency. Folic acid deficiency can cause 15 anemia in the mother and birth defects in the fetus. The invention also provides a nutritional regimen for optimizing the absorption of folio acid in pregnant women. The regimen comprises a stable chewable or quickly dissolving form comprising a non-toxic acid 20 neutralizing alkaline compound surrounding a folic acid compound or derivative thereof, so that the folic acid comacund is microencacsulated. The form is selected from the group consisting of a chewable tablet, a quick 30 WO00/66083 PCTUS00/1 1688 dissolve tablet, an effervescent tablet, a particular matrix, a microparticulate matrix and mixtures thereof. The invention also provides a nutritional regimen for optimizing absorption of folic acid in an animal 5 comprising a stable chewable form comprising a non toxic acid neutralizing alkaline compound selected from the group consisting of calcium based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based 10 compounds, and mixtures thereof surrounding a folic acid compound or derivative thereof. The non-toxic acid neutralizing compound has a total daily dosage of at least 2 meq of acid neutralizing capacity. The folic acid compound or derivative has a total daily 15 dosage of greater than 450 mca. The method of preventing or treating folio acid deficiency in a pregnant woman comprises administering at least once during a day to the pregnant woman a stable chewable or quickly dissolvable form. The form 20 comprises a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound.
WO00/66083 PCTUS00/1 1688 The total dosage of the folio acid compound or derivative thereof administered during the day is at least 500 mcg. The total dosage of non-toxic acid neutralizing alkaline compound administered during the 5 day is at least 2 meq of acid neutralizing capacity. The invention also provides a method of preventing or treating folio acid deficiency in an animal. The animal can be male or a pregnant or non-pregnant female. The method comprises administering at least 10 once during a day to the animal a stable chewable or dissolvable form. The form comprises a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound and a non-folate biologically active substance. 15 The present invention also comprises a method of preventing or treating a condition in an animal by administering the present compositions to said animal. Any physiological condition or the like could be targeted by use 0of the present compositions. 20 Preferably, the condition would be a phnysiological condition in which l-c acid Is imclicated, without limitation. 32 WO00/66083 PCT/US00/ 1688 The present invention contemplates the use of pharmaceutically acceptable carriers which may be prepared from a wide range of materials. Without being limited thereto, such materials include diluents, 5 binders and adhesives, lubricants, plasticizers, disintegrants, colorants, bulking substances, flavorings, sweeteners and miscellaneous materials such as buffers and adsorbents in order to prepare a particular medicated composition. 10 Binders may be selected from a wide range of materials such as hydroxypropylmethylcellulose, ethylcellulose, or other suitable cellulose derivatives, povidone, acrylic and methacrylic acid co polymers, pharmaceutical glaze, gums, milk derivatives, 15 such as whey, starches, and derivatives, as well as other conventional binders well known to persons skilled in the art. Exemplary non-limiting solvents are water, ethanol, isopropyl alcohol, methylene chloride or mixtures and combinations thereof. 20 Exemplary non-limiting bulking substances include sugar, lactose, gelatin, starch, and silicon dioxide. The clasticizers used in the dissolution modifying system are preferably previouslv'y dissolved in an WO00/66083 PCTUS00/1 1688 organic solvent and added in solution form. Preferred plasticizers may be selected from the group consisting of diethyl phthalate, diethyl sebacate, triethyl citrate, cronotic acid, propylene glycol, butyl 5 phthalate, dibutyl sebacate, caster oil and mixtures thereof, without limitation. As is evident, the plasticizers may be hydrophobic as well as hydrophilic in nature. water-nscluable hydrophobic substances, such as diethyl phthalate, diethyl sebacate and caster 10 oil are used to delay the release of water-soluble vitamins, such as vitamin B 6 and vitamin C. In contrast, hydrophilic plasticizers are used when water insoluble vitamins are employed which aid in dissolving the encapsulated film, making channels in the surface, 15 which aid in nutritional composition release. The dosage forms of the present invention may involve the administration of a nutritional composition in a single dose during a 24 hour period cf: ime, a double dose during a 24 hour period of time, or 20 multiple doses, e.g., more than two doses during a 24 hour period of time. The double or multiple doses may be taken simultaneously or at different times during the 24 hour period.
WO00/66083 PCTUS00/1 1688 The compositions of the present invention are intended for use by both males and females. The dosages are adjusted according to body weight to compensate, at least partially, for differences in male 5 and female physiological need. The compositions are particularly suitable for individuals having enhanced folic acid requirements, for example, pregnant women, without limitation. Moreover, the formulations can be further adapted based upon the specific needs, genetic 10 predispositions or identified deficiencies of an individual. The foregoing is considered as illustrative only of the principles of the invention. Further, since numerous modifications and changes will readily occur 15 to those skilled in the art, it is not desredc to limit the invention to the exact construction and operation shown and described, and accordingly all suitable modifications and equivalents may be resorted to, falling within the scope of the invention. 20 The following examples are illustrative of prererrec emodimentrs or the invention and are not to be construed as limitzing the invention thereto.
WO00/66083 PCTIUS00/1 1688 EXAMPLE I Preparation of Multi-Vitamin and Mineral Sunclements The following compositions are used to prepare 5 chewable or dissolvable folic acid supplements for administration to males or females: Table I Component Formula I (mg) Formula II (mg) Folic Acid 0.45 1.0 10 Calcium 150
--
Carbonate Aluminum 150 200 Hydroxide Compressible 500 600 15 Sugar Flavoring 40 80 Magnesium 3.5 9 Stearate 20 Example II The focowIng compos~ions are used to prepare chewable or dissolvable folic acid supplements. 25 WO00/66083 PCTUS00/1 1688 Table II Component Ranges (mg) Folic Acid 0.45-1.0 Calcium Carbonate 100-1,000 5 Aluminum Hydroxide 150-200 Compressible Sugar 500-600 Flavoring 40-80 Magnesium Stearate 3.5-9 10 Chewable or dissolvable tablets incorporating the above formulations are prepared using conventional methods and materials known in the pharmaceutical art. The resulting folic acid supplement tablets are 15 recovered and stored for further use. Example III A chewable folic acid supplement as set forth herein may be prepared, as follows: 20 First, combine a compressible sugar with folic acid in a blender and blend until- a uniform folic acid/sugar mixture is formed. Next, combine a WO00/66083 PCTUS00/1 1688 flavoring, a colorant and calcium carbonate with the folic-acid/ sugar mixture and blend until a uniform folic acid/calcium carbonate mixture is formed. Then, to the folic acid/calcium carbonate mixture, add 5 magnesium stearate and blend until uniformity is attained to form a lubricated folic acid/calcium carbonate mixture. The lubricated folic acid/acid neutralizing mixture is then compressed into a tablet using conventional methods. 10 Example IV A chewable folic acid supplement as set forth herein may further be prepared, as follows: First, combine a compressible sugar with folic 15 acid in a blender and blend until a uniform folic acid/sugar mixture is formed. Next, add a flavoring, a colorant and aluminum hydroxide to the folic acid/sugar mixture and blend until a uniform folic acid/aluminum hydroxide mixture is formed. Then, to 20 the folic acid/aluminum hydroxide mixture, add magnesium stearate and blend until uniformityv is attained to form a lubricated folic acid/aluminum hydroxide mixture. The lubricated folic acid/aluminum 38 WO00/66083 PCTUS00/11688 hydroxide mixture is then compressed into a tablet using conventional methods. Example V 5 A dissolvable folic acid supplement as set forth herein may be prepared, as follows: First, combine folic acid with a compressible sugar in a blender and blend until uniformity is achieved to form a uniform compressible sugar/folic 10 acid mixture. Next, add to the compressible sugar/folic acid mixture a coloring agent, a flavoring agent and calcium carbonate and blend until a uniform folic acid/calcium carbonate mixture is attained. Then, combine the folic acid/calcium carbonate mixture 15 with hydroxypropylmethylcellulose and blend to form a uniform dissolvable mixture. Finally, compress the dissolvable mixture to form a tablet that will disintegrate within 30 seconds after oral ingestion. 20 The invention being thus described, it will be apparent that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all 39 WO00/66083 PCTUS00/1 1688 such modifications are intended to be within the scope of the appended claims. 40
Claims (46)
1. A nutritional supplement for optimizing absorption of folic acid in an animal, which comprises: a stable chewable or dissolvable form comprising 5 a non-toxic acid neutralizing alkaline compound combined with a folic acid compound or derivative thereof; wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at least 2 meq of 10 acid neutralizing capacity, and the folic acid compound or derivative thereof has a total daily dosage of at least 450 mcg.
2. The nutritional supplement of claim 1, wherein 15 said non-toxic acid neutralizing alkaline compound surrounds said folic acid compound or derivative thereof.
3. The nutritional supplement of claim 1, wherein 20 said non-toxic acid neutralizing alkaline compound is selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds,
11- WO00/66083 PCTUS00/I 1688 magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof. 4. The nutritional supplement of claim 1, wherein 5 said non-toxic acid neutralizing alkaline compound is selected from the group consisting of aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum hydroxy carbonate, aluminum citrate, dihydroxyaluminum sodium carbonate, aluminum magnesium 10 glycinate, dihydroxyaluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, calcium hydroxide, calcium phosphate, calcium citrate, 15 calcium citrate malate, hydrated magnesium aluminate, activated sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, potassium carbonate, potassium 20 phosphate, potassium citrate, sodium carbonate, sodium bicarbonate, sodium chosohate, sodium citrate and mixtures ohereof. I 2 WO00/66083 PCTUS00/11688 5. The nutritional supplement of claim 1, wherein said chewable or dissolvable form is selected from the group consisting of a chewable tablet, a quick dissolve tablet, an effervescent tablet, a particulate matrix, 5 a microparticulate matrix and mixtures thereof. 6. The nutritional supplement of claim 1, wherein said folic acid compound or derivative thereof is microencapsulated. 10 7. The nutritional supplement of claim 1, wherein said nutritional supplement is administered at least once a day. 15 8. The nutritional supplement of claim I, wherein said nutritional supplement is administered at least twice a day. 9. The nutritional supplement of claim I, wherein 20 said animal is of a female gender. 10. The nutritional supplement of claim 1, wherein said animal is a pregnant female. 43 WO00/66083 PCTUS00/l 1688 11. The nutritional supplement of claim 1, wherein said animal is a mammal.
12. The nutritional supplement of claim 1, 5 wherein said animal is a non-pregnant female.
13. The nutritional supplemen: of claim 1, wherein said animal is of a male gender. 10 14. A nutritional supplement for optimizing absorption of a folic acid compound or derivative thereof in an animal, which comprises: a stable chewable or dissolvable form comprising a non-toxic acid neutralizing alkaline compound 15 surrounding a folic acid compound or derivative thereof; wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at _ eas: 2 mea of acid neutralizing caacity, and the folic acid compound 20 or derivative there has a to.al daily dosage of at least 450 mc. WO00/66083 PCTUS00/1 1688
15. The nutritional supplement of claim 14, wherein said non-toxic acid neutralizing alkaline compound is selected from the group consisting of calcium-based compounds, antacids, aluminum-based 5 compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof.
16. The nutritional supplement of claim 14, 10 wherein said non-toxic acid neutralizing alkaline compound is selected from the group consisting of aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum hydroxy carbonate, aluminum citrate, dihydroxyaluminum sodium carbonate, aluminum 15 magnesium glycinate, dihydroxyaluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, calcium hydroxide, calcium phosphate, calcium citrate, 20 calcium citrate malate, hydrated magnesium aluminate, activated sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium WO00/66083 PCTUS00/1 1688 glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, potassium carbonate, potassium phosphate, potassium citrate, sodium carbonate, sodium bicarbonate, sodium phosphate, sodium citrate and 5 mixtures thereof.
17. The nutritional supplement of claim 14, wherein said chewable or dissolvable form is selected from the group consisting of a chewable tablet, a quick 10 dissolve tablet, an effervescent tablet, a particulate matrix, a microparticulate matrix and mixtures thereof.
18. The nutritional supplement of claim 14, wherein said folic acid compound or derivative thereof 15 is microencacsulated.
19. The nutritional supplement of claim 14, wherein said nutritional supplement is administered at least once a day. 20 46 WO 00/66083 PCTUS00/1 1688
20. The nutritional supplement of claim 14, wherein said nutritional supplement is administered at least twice a day. 5 21. The nutritional supplement of claim 14, wherein said animal is of a female gender.
22. The nutritional supplement of claim 14, wherein said animal is a pregnant female. 10
23. The nutritional supplement of claim 14, wherein said animal is a non-pregnant female.
24. A prenatal nutritional supplement for 15 optimizing absorption of folic acid in a pregnant woman, which comprises: a stable chewable or dissolvable form comprising a non-toxic acid neutralizing alkaline compound surrounding a folic acid compound or derivative 20 thereof; wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at least 2 meq of 47 WO00/66083 PCTUS00/I 1688 acid neutralizing capacity, and the folic acid compound or derivative thereof has a total daily dosage of at least 500 mcg. 5 25. A nutritional regimen for optimizing absorption of folic acid in a pregnant woman, which comprises: stable chewable or dissolvable form comprising a non-toxic acid neutralizing alkaline compound 10 surrounding a folic acid compound or derivative thereof; wherein the non-toxic acid neutralizing alkaline compound is present in said regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, 15 and the folic acid compound or derivative thereof is present in said regimen in a total daily dosage of at least 450 mcg.
26. The nutritional supplement of claim 25, 20 wherein said non-toxic acid neutralizing alkaline compound is selected from the group consisting of calcium-based compounds, antacids, aluminum-based 48 WO00/66083 PCTUS00/1 1688 compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof. 5 27. The nutritional supplement of claim 25, wherein said non-toxic acid neutralizing alkaline compound is selected from the group consisting of aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum hydroxy carbonate, aluminum 10 citrate, dihydroxyaluminum sodium carbonate, aluminum magnesium glycinate, dihydroxyaluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth subnitrate, calcium carbonate, 15 calcium hydroxide, calcium phosphate, calcium citrate, calcium citrate malate, hydrated magnesium aluminate, activated sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, 20 magnesium trisilicate, potassium carbonate, potassium phosphate, potassium citrate, sodium carbonate, sodium 49 WO00/66083 PCTUS00/11688 bicarbonate, sodium phosphate, sodium citrate and mixtures thereof.
28. The nutritional supplement of claim 25, 5 wherein said chewable or dissolvable form is-selected from the group consisting of a chewable tablet, a quick dissolve tablet, an effervescent tablet, a particulate matrix, a microcarticulate matrix and mixtures thereof. 10 29. The nutritional supplement of claim 25, wherein said folic acid compound or derivative thereof is microencaosulated.
30. The nutritional sucolement of claim 2 , 15 wherein said nutritional supplement is administered at least once a day.
31. The nutritional suo±lement of claim 25, wherein said nutritional suppcolement is administered at 20 least twice a day. 50, WO00/66083 PCTUS00/1 1688
32. A prenatal chewable nutritional supplement for optimizing absorption of folio acid in a pregnant woman, which comprises: a stable chewable form comprising a non-toxic acid 5 neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof surrounding a folic acid compound or 10 derivative thereof; wherein the non-toxic acid neutralizing alkaline compound has a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound or derivative thereof has a total daily dosage of at 15 least 500 mca.
33. A nutritional regimen for optimizing absorption of folic acid in an animal, which comprises: stable chewable form comprising a non-toxic acid 20 neutralizina alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, WO00/66083 PCTUS00/11688 sodium-based compounds, potassium-based compounds, and mixtures thereof surrounding a folic acid compound or derivative thereof; wherein the non-toxic acid neutralizing alkaline 5 compound is present in said regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound or derivative thereof is present in said regimen in a total daily dosage of at least 450 mcg. 10
34. The nutritional regimen of claim 33, wherein said animal is a mammal.
35. The nutritional regimen of claim 33, wherein 15 said animal is a pregnant female.
36. The nutritional regimen of claim 33, wherein said animal is a non-pregnant female. 20 37. The nutritional regimen of claim 33, wherein said animal is a male animal. WO00/66083 PCTUS00/1 1688
38. A nutritional regimen for optimizing absorption of folic acid in a pregnant woman, which comprises: stable chewable form comprising a non-toxic acid 5 neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof surrounding a folic acid compound or 10 derivative thereof; wherein the non-toxic acid neutralizing alkaline compound is present in said regimen in a total daily dosage of at least 2 meq of acid neutralizing capacity, and the folic acid compound or derivative thereof is 15 present in said regimen in a total daily dosage of at least 500 mcg.
39. A method of optimizing the absorption of folic acid administered to an animal in a nutritional 20 supplement, which comprises: administering at least once during a day to the animal a stable chewable or dissolvable form comprising 53 - WO00/66083 PCTUS00/I 1688 a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound; wherein the total dosage of said folic acid 5 compound or derivative thereof administered during the day is at least 450 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 10
40. The method of claim 39, wherein said animal is a mammal.
41. The method of claim 39, wherein said animal 15 is of a female gender.
42. The method of claim 39, wherein said animal is a pregnant female. 20 43. The method of claim 39, wherein said animal is a non-pregnant female. 54 WO00/66083 PCTUS00/1 1688
44. The method of claim 39, wherein said animal is of a male gender.
45. The method of claim 39, wherein said non 5 toxic acid neutralizing alkaline compound is selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and mixtures thereof. 10
46. The method of claim 39, wherein said non toxic acid neutralizing alkaline compound is selected from the group consisting of aluminum carbonate, aluminum hydroxide, aluminum phosphate, aluminum 15 hydroxy carbonate, aluminum citrate, dihydroxyaluminum sodium carbonate, aluminum magnesium glycinate, dihydroxyaluminum aminoacetate, dihydroxyaluminum aminoacetic acid, bismuth aluminate, bismuth carbonate, bismuth subcarbonate, bismuth subgallate, bismuth 20 subnitrate, calcium carbonate, calcium hydroxide, calcium phosphate, calcium citrate, calcium citrate malate, hydrated magnesium aluminate, activated WO00/66083 PCT/US00/1I1688 sulfate, magnesium aluminate, magnesium aluminosilicates, magnesium carbonate, magnesium glycinate, magnesium hydroxide, magnesium oxide, magnesium trisilicate, potassium carbonate, potassium 5 phosphate, potassium citrate, sodium-carbonate, sodium bicarbonate, sodium phosphate, sodium citrate and mixtures thereof.
47. The method of claim 39, wherein said chewable 10 or dissolvable form is selected from the group consisting of a chewable tablet, a quick dissolve tablet, an effervescent tablet, a particulate matrix, a microparticulate matrix and mixtures thereof. 15 48. The method of claim 39, wherein said folic acid compound or derivative thereof is microencapsulated.
49. The method of claim 39, wherein said 20 nutritional supplement is administered at least once a day. D6 WO00/66083 PCTUS00/1 1688
50. The method of claim 39, wherein said nutritional supplement is administered at least twice a day. 5
51. A method of optimizing the absorption of folic acid administered to a pregnant woman in a nutritional supplement, which comprises: administering at least once during a day to the pregnant woman a stable chewable or dissolvable form 10 comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound; wherein the total dosage of said folic acid compound or derivative thereof administered during the 15 day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 20
52. A method of preventing or treating folic acid deficiency in a pregnant woman, which comprises: D7 WO00/66083 PCTUS00/1 1688 administering at least once during a day to the pregnant woman a stable chewable or dissolvable form comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing 5 alkaline compound; wherein the total dosage of said folic acid compound or derivative thereof administered during the day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound 10 administered during the day has at least 2 meq of acid neutralizing capacity.
53. A method of preventing or treating folic acid deficiency in an animal, which comprises: 15 administering at least once during a day to the pregnant woman a stable chewable or dissolvable form comprising a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound and a non-folate biologically active 20 substance; wherein the total dosage of said folic acid compound or derivative thereof administered during the 58 WO00/66083 PCTUS00/1 1688 day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 5
54. The method of claim 53, wherein said animal is of a female gender.
55. The method of claim 53, wherein said animal 10 is a pregnant female.
56. The method of claim 53, wherein said animal is a non-pregnant female. 15
57. The method of claim 53, wherein said animal is of a male gender.
58. A method of optimizing the absorption of folic acid administered to an animal in a nutritional 20 supplement, which comprises: administering at least once during a day to the mammal a stable chewable form comprising a folic acid 59 WO00/66083 PCTIUS00/I 1688 compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based 5 compounds, sodium-based compounds, potassium-based compounds and mixtures thereof; wherein the total dosage of said folic acid compound or derivative thereof administered during the day is at least 450 mcg, and the total dosage of said 10 non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity.
59. A method of optimizing the absorption of 15 folic acid administered to a pregnant woman in a nutritional supplement, which comprises: administering at least once during a day to the pregnant woman a stable chewable form comprising a folic acid compound or derivative thereof in 20 combination with a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium based compounds, antacids, aluminum-based compounds, 60 WO00/66083 PCT/US00/1 1688 magnesium-based compounds, sodium-based compounds, potassium-based compounds and mixtures thereof; wherein the total dosage of said folic acid compound or derivative thereof administered during the 5 day is greater than 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 10 60. A method of preventing or treating folic acid deficiency in a pregnant woman, which comprises: administering at least once during a day to the pregnant woman a stable chewable form comprising a folic acid compound or derivative thereof in 15 combination with a non-toxic acid neutralizing alkaline compound selected from the group consisting cf calcium based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, cotassium-based comounds and mixtures thereof; 20 wherein the total dosage of said folic acid compound or derivat i ve thereof administered durin g . the day is at least 500 mcg, and the total dosage of said 0! WO00/66083 PCT/US00/1 1688 non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. 5
61. A method of preventing or treating folic acid deficiency in a pregnant woman, which comprises: administering at least once during a day to the pregnant woman a stable chewable form comprising a folic acid compound in combination with a non-folate 10 biologically active substance and a non-toxic acid neutralizing alkaline compound selected from the group consisting of calcium-based compounds, antacids, aluminum-based compounds, magnesium-based compounds, sodium-based compounds, potassium-based compounds, and 15 mixtures thereof; wherein the total dosage of said folic acid administered during the day is at least 500 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at 20 least 2 mea of acid neutralizing capacity. 62 WO00/66083 PCTUS00/1 1688
62. A method of preventing or treating a condition in an animal, which comprises: administering at least once during a day to the animal a stable chewable or dissolvable form comprising 5 a folic acid compound or derivative thereof in combination with a non-toxic acid neutralizing alkaline compound; wherein the total dosage of said folic acid compound or derivative thereof administered during the 10 day is at least 450 mcg, and the total dosage of said non-toxic acid neutralizing alkaline compound administered during the day has at least 2 meq of acid neutralizing capacity. C'3
Applications Claiming Priority (3)
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|---|---|---|---|
| US09/303000 | 1999-04-30 | ||
| US09/303,000 US6261600B1 (en) | 1999-04-30 | 1999-04-30 | Folic acid supplement |
| PCT/US2000/011688 WO2000066083A1 (en) | 1999-04-30 | 2000-04-28 | Folic acid supplement |
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| AU4977700A true AU4977700A (en) | 2000-11-17 |
| AU777261B2 AU777261B2 (en) | 2004-10-07 |
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| EP (2) | EP1175203A4 (en) |
| JP (1) | JP2002543107A (en) |
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| BR (1) | BR0010189A (en) |
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| CA2313504C (en) | 1999-07-12 | 2007-05-29 | Douglas P. Debernardi | Folic acid in solid dosage forms |
| US9357797B2 (en) | 1999-11-06 | 2016-06-07 | Janmarie Hornack | Dietary supplement containing alkaline electrolyte buffers |
| US20030235629A1 (en) * | 1999-11-06 | 2003-12-25 | Janmarie Hornack | Dietary supplement containing alkaline electrolyte buffers |
| US6887926B1 (en) | 2001-11-16 | 2005-05-03 | Oatey Co. | Bonding compositions for chlorinated polymers and methods of using the same |
| US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
| US8790637B2 (en) | 2003-06-27 | 2014-07-29 | DePuy Synthes Products, LLC | Repair and regeneration of ocular tissue using postpartum-derived cells |
| PL1641914T3 (en) | 2003-06-27 | 2017-01-31 | DePuy Synthes Products, Inc. | Postpartum cells derived from placental tissue, and methods of making and using the same |
| AU2006202209B2 (en) * | 2005-05-27 | 2011-04-14 | Lifescan, Inc. | Amniotic fluid derived cells |
| US7901710B2 (en) | 2005-08-04 | 2011-03-08 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
| US8263137B2 (en) | 2005-08-04 | 2012-09-11 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
| US7998500B2 (en) | 2005-08-04 | 2011-08-16 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for women |
| US8202546B2 (en) | 2005-08-04 | 2012-06-19 | Vertical Pharmaceuticals, Inc. | Nutritional supplement for use under physiologically stressful conditions |
| US7767248B2 (en) * | 2007-02-02 | 2010-08-03 | Overly Iii Harry J | Soft chew confectionary with high fiber and sugar content and method for making same |
| US20090011079A1 (en) * | 2007-07-02 | 2009-01-08 | Bestsweet, Inc. | Hard Coated Confectionary Having A Consumable Soft Chewing Core With An Active And Method For Making Same |
| US9125844B1 (en) | 2007-09-25 | 2015-09-08 | Argent Development Group, Llc | Nutritional supplements for women desiring to become pregnant, and pregnant and nursing women |
| US7964189B1 (en) | 2007-09-25 | 2011-06-21 | Argent Development Group, Llc | Nutritional supplements for women desiring to become pregnant, and pregnant and nursing women |
| US8535660B1 (en) | 2008-05-27 | 2013-09-17 | Argent Development Group, Llc | Nutritional supplements for pregnant women |
| US8535659B1 (en) | 2008-05-27 | 2013-09-17 | Argent Development Group, Llc | Nutritional supplements for pregnant women |
| JP2015030690A (en) * | 2013-08-01 | 2015-02-16 | 東洋精糖株式会社 | Composition with improved bioabsorbability of pteridine derivative and bioabsorbency promoter |
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| GB8410290D0 (en) | 1984-04-19 | 1984-05-31 | Callingham B A | Pharmaceutical compositions |
| IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
| NL8403433A (en) | 1984-11-09 | 1986-06-02 | Holland Melkunie | FOOD SUPPLY PREPARATION BASED ON MILK COMPONENTS. |
| US4752479A (en) | 1986-05-27 | 1988-06-21 | Ciba-Geigy Corporaton | Multi vitamin and mineral dietary supplement with controlled release bioavailable iron |
| SU1653714A1 (en) * | 1988-03-17 | 1991-06-07 | Всесоюзный Научно-Исследовательский Институт Коневодства | Method of feeding sporting horses |
| ATE128027T1 (en) * | 1991-07-01 | 1995-10-15 | Gergely Gerhard | SUCKING OR CHEWABLE TABLET. |
| US5215750A (en) * | 1991-09-04 | 1993-06-01 | Keane Ii Michael A | L-glutamine and vitamin-containing compositions effective for inducing weight loss and for weight control |
| AU5162793A (en) | 1992-09-23 | 1994-04-12 | Kv Pharmaceutical Corporation | Multi-vitamin and mineral supplement for pregnant women |
| FR2705208B1 (en) | 1993-05-17 | 1995-07-28 | Roquette Freres | Sugar-free coating process and products obtained according to the process. |
| US5895664A (en) * | 1993-09-10 | 1999-04-20 | Fuisz Technologies Ltd. | Process for forming quickly dispersing comestible unit and product therefrom |
| FR2723682B1 (en) * | 1994-08-19 | 1996-09-27 | Boiron | ABSORBABLE NUTRITIONAL SUPPLEMENT FOR THE DAILY BALANCE OF CHILDREN AND ADOLESCENTS. |
| US5733575A (en) | 1994-10-07 | 1998-03-31 | Bpsi Holdings, Inc. | Enteric film coating compositions, method of coating therewith, and coated forms |
| US5569477A (en) | 1995-04-28 | 1996-10-29 | Mccready Consumer Products, Inc. | Chewing gum containing vitamins or other active materials |
| EP0831728A2 (en) * | 1995-06-06 | 1998-04-01 | Campbell Soup Company | Mineral supplements for dietetic food |
| DE29723190U1 (en) * | 1996-01-20 | 1998-08-06 | NPE Natur Pharma Ernährungsprodukte GmbH, 33602 Bielefeld | Confectionery |
| JP3602141B2 (en) * | 1996-01-31 | 2004-12-15 | サウス、アラバマ、メディカル、サイエンス、ファウンデーション | Food and vitamin preparations containing natural isomers of reduced folate |
| US5895652A (en) * | 1996-07-29 | 1999-04-20 | Longevity Institute International | Method of metabolic adjuvanation and cellular repair |
| CA2261764A1 (en) * | 1996-07-30 | 1998-02-05 | Jeffrey B. Blumberg | Dietary supplements |
| AU4398897A (en) * | 1996-10-03 | 1998-04-24 | Taiyo Kagaku Co. Ltd. | Mineral composition |
| JPH10287560A (en) * | 1997-04-11 | 1998-10-27 | Taisho Pharmaceut Co Ltd | Pharmaceutical composition |
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- 2000-04-28 JP JP2000614969A patent/JP2002543107A/en active Pending
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| AU777261B2 (en) | 2004-10-07 |
| US6261600B1 (en) | 2001-07-17 |
| EP1857102A1 (en) | 2007-11-21 |
| CA2372229A1 (en) | 2000-11-09 |
| WO2000066083A1 (en) | 2000-11-09 |
| EP1175203A1 (en) | 2002-01-30 |
| EP1175203A4 (en) | 2004-02-25 |
| BR0010189A (en) | 2002-07-02 |
| JP2002543107A (en) | 2002-12-17 |
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